A PHASE 1, OPEN-LABEL, DOSE ESCALATION STUDY OF PF-04518600 AS A SINGLE
AGENT AND IN COMBINATION WITH PF-05082566 IN PATIENTS WITH SELECTED
LOCALLY ADVANCED OR METASTATIC CANCERS

The goal of this clinical research study is to learn about the effects
of the study drugs, PF-04518600 and PF-05082566, and to find out what
side effects occur when PF-04518600 is given alone or in combination
with PF-05082566. Researchers also want to learn: how long the study
drug(s) stay in the body, if the body makes antibodies (substances that
are created by the immune system and may attack foreign cells or
substances) against the study drug, if the study drug(s) affect your
immune system, and if the study drug(s) can help to control the disease.
PF-04518600 and PF-05082566 are types of molecules called monoclonal
antibodies (mAb). These particular monoclonal antibodies are designed
to trigger the immune system to attack tumor cells.

1) Part A Monotherapy (Part A1 only): Patients with histological or
cytological diagnosis of HNSCC, HCC, melanoma, or RCC who progressed on
or are intolerant to standard therapy, for which no standard therapy is
available or who decline standard therapy.
2) Part A Monotherapy (Part A2 only): Patients with histological or
cytological diagnosis of HCC 1) have had 0 to 2 prior line of systemic
therapy (progressed or intolerant to approved HCC standard of care
treatment [ie sorafenib or regorafenib]) and 2) who have not received
prior anti-PD-L1/PD-1 therapy unless it has been approved as a standard
of care for HCC.
3) Part B Combination Therapy (Part B1 only): Patients with histological
or cytological diagnosis of NSCLC, HNSCC, melanoma, urothelial bladder
carcinoma (including renal pelvis, ureters, urinary ladder, and
urethra), gastric or squamous cell carcinoma of the uterine cervix who
progressed on or are intolerant to standard therapy, for which no
standard therapy is available, or who decline standard therapy.
4) Part B Combination Therapy (Part B2 Arm 1 only): a.) Ocular melanoma;
and have received no more than one line of systemic therapy for
metastatic disease. Patients must not have received immune modifying
agents (eg. anti-PD-L1, anti-PD1, anti-CTLA4, TNF agonist, etc.) for
metastatic disease. or b.) Cutaneous/acral melanoma; and have 1) only
previously received systemic therapy for advanced/metastatic disease
with the following therapies: BRAF and MEK inhibitors, anti-PD-L1,
anti-PD-1, or anti-CTLA4 and 2) have received checkpoint inhibitor
(anti-PD-L1, anti-PD-1, or anti-CTLA4) based treatment as most recent
line of therapy on which disease progressed, as long as progression did
not occur in the first 3 months of receiving checkpoint inhibitor treatment.
5) Part B Combination Therapy (Part B2 Arm 2 only): Histological or
cytological diagnosis of NSCLC. Patients must have A) previously
received prior anti-PD-L1 or anti-PD-1 mAb as most recent therapy, AND
B) did not have progressive disease as best overall response on recent
PD-L1/PD-1 therapy, AND C) who subsequently progressed on anti-PD-L1 or
anti-PD-1 mAb.
6) (Part A & Part B): Patients must have at least one measurable
lesion as defined by RECIST version 1.1 be willing to undergo the
mandatory biopsies and there is no excessive risk from biopsy as judged
by the Investigator.
7) (Part A & Part B): Adults (men and women) age >/=18 years (
for Japan only : >/= 20 years of age)
8) (Part A & Part B): Eastern Cooperative Oncology Group (ECOG)
Performance Status (PS) 0 or 1.
9) (Part A & Part B): Adequate Bone Marrow Function, including: ANC
>/=1,500/mm^3 or >/=1.5 x 10^9/L. Platelets >/=100,000/mm^3 or
>/=100 x 10^9/L. (Part A only) Platelets for HCC only:
>/=60,000/mm^3. Hemoglobin >/=9 g/dL. Limited transfusions to
reach this value are allowed, after discussion with sponsor’s medical
monitor. There should not be a chronic need for transfusions in the
recent (approximately 3 month) past.
10) (Part A & Part B): Adequate Renal Function, including: Serum
creatinine </=1.5 x upper limit of normal (ULN) or estimated
creatinine clearance >/=60 ml/min as calculated using the method
standard for the institution. If an estimated creatinine clearance is
believed to be inaccurate for a patient, 24 hr urine collection with
actual assessment of creatinine clearance is allowed.
11) (Part A & Part B): Adequate Liver Function (all patients, except
HCC, see Inclusion Criteria 9), including: Total serum bilirubin
</=1.5 x ULN unless the patient has documented Gilbert syndrome.
Aspartate and alanine aminotransferase (AST & ALT) </=2.5 x ULN;
(Part A only) </=5.0 x ULN if there is liver involvement secondary to tumor.
12) (Part A only): Inclusion for HCC patients only: Child-Pugh Class A
or B with a score of 7 and no prior history of hepatic encephalopathy.
Serum bilirubin </=3 mg/dL. Serum Albumin >/=2.8 g/dL. AST and ALT
</=5.0 x ULN. Amylase and lipase <1.5 ULN. International
Normalized Ratio (INR) </=2.3 or Prothrombin Time (PT) </=6
seconds above control.
13) (Part A & Part B): Resolved acute effects of any prior therapy
to baseline severity or Grade </=T1 CTCAE except for AEs not
constituting a safety risk by investigator judgment.
14) (Part A & Part B): Serum or urine pregnancy test (for women of
childbearing potential) negative at screening and at the baseline visit
before the patient may receive the investigational product).
15) (Part A & Part B): Male and female patients of childbearing
potential and at risk for pregnancy must agree to use two highly
effective method(s) of contraception throughout the study and for at
least 90 days after the last dose of assigned treatment. Female patients
who are not of childbearing potential as defined below, are eligible to
be included (ie, meet at least one of the following criteria): Have
undergone a documented hysterectomy and/or bilateral oophorectomy. Have
medically confirmed ovarian failure; or Achieved postmenopausal status,
defined as follows: cessation of regular menses for at least 12
consecutive months with no alternative pathological or physiological
cause; a serum follicle stimulating hormone (FSH) level within the
laboratory's reference range for postmenopausal women.
16) (Part A & Part B): Evidence of a personally signed and dated
informed consent document indicating that the patient has been informed
of all pertinent aspects of the study.
17) (Part A & Part B): Patients who are willing and able to comply
with scheduled visits, treatment plans, laboratory tests and other procedures.

Exclusion:

1) Part A Monotherapy (Part A only): Patients with known symptomatic
brain metastases requiring systemic corticosteroids. Patients with
previously diagnosed brain metastases are eligible if they have
completed their treatment and have recovered from the acute effects of
radiation therapy or surgery prior to the start of study medication,
have discontinued corticosteroid treatment for these metastases for at
least 4 weeks and are neurologically stable. Mild neurological deficits
are allowed, if they do not interfere with the ability to judge the
safety profile of PF-04518600/utomilumab.
2) Part B Combination Therapy (Part B only): Patients with known
symptomatic brain metastases requiring systemic corticosteroids.
Patients with previously diagnosed brain metastases are eligible if they
have completed their treatment and have recovered from the acute effects
of radiation therapy or surgery prior to the start of study medication,
have discontinued corticosteroid treatment for these metastases for at
least 4 weeks and are neurologically stable. Mild neurological deficits
are allowed, if they do not interfere with the ability to judge the
safety profile of PF-04518600 / utomilmumab.
3) (Part A & Part B): History of or active autoimmune disorders
(including but not limited to: Crohn’s Disease, rheumatoid arthritis,
scleroderma, systemic lupus erythematosus, Grave’s disease) and other
conditions that compromise or impair the immune system.
4) (Part A & Part B): Active bacterial, fungal or viral infection
including hepatitis B (HBV, see exception below for patients with HCC),
hepatitis C (HCV), known human immunodeficiency virus (HIV) or acquired
immunodeficiency syndrome (AIDS) -related illness. For Part A1 patients
with HCC only: after the safety profile of a cohort has been established
in 2-4 patients, and escalation to the next higher dose level has taken
place, HCC patients enrolled into the expansion lower dose cohort
meeting the following criteria can be enrolled: patients infected with
the HBV or HCV but with minimal viral load (<20 IU/ml) at the moment
of screening and who are being treated with either entecavir or
tenofovir during the full study period. For Part A2 HCC patients:
patients with chronic HCV infection are allowed; however, patients with
chronic HBV infection must be receiving effective antiviral therapy
(viral load <100 IU/ml).
5) (Part A & Part B) (Continuation from #4): Patients with active
coinfection with HBV and HCV, active coinfection with HBV and hepatitis
D virus are excluded. The following HCC subtypes are also exclusionary:
fibrolamellar HCC, sarcomatoid HCC, and mixed cholangiocarcinoma.
6) (Part A & Part B): Bleeding esophageal or gastric varices <2
months prior to informed consent document (ICD) date.
7) (Part A & Part B): Unmanageable ascites (limited medical
treatment to control ascites is permitted, but all patients with ascites
will require review by sponsor’s medical monitor).
8) (Part A & Part B): Major surgery within 4 weeks of starting study treatment.
9) (Part A & Part B Combination): Patients who have undergone solid
organ or hematopoietic transplant.
10) (Part A & Part B): Systemic anti-cancer therapy within 4 weeks
of starting study treatment (6 weeks for mitomycin C or nitrosoureas).
If systemic anti-cancer therapy was given within 4 weeks, patient may be
included if 4-5 times elimination half-life of drug has passed.
11) (Part A & Part B): Radiation therapy within 4 weeks of starting
study treatment, except: palliative radiotherapy to a limited field is
allowed after consultation with sponsor’s medical monitor at any time
during study participation, including during screening.
12) (Part A & Part B): Previous high dose chemotherapy requiring
stem cell rescue.
13) (Part A only): Prior treatment with an OX40 agonist.
14) (Part B only): Prior treatment with an OX40 agonist or a 4 - 1 BB agonist.
15) (Part A & Part B): Currently require doses of systemic immune
suppressive medication [eg, >/=10 mg of prednisone or equivalent
(>/=1.5 mg of dexamethasone)].
16) (Part A & Part B): History of Grade 3 or higher immune-mediated
adverse event (including AST/ALT elevations that where considered drug
related and cytokine release syndrome) that was considered related to
prior immune-modulatory therapy (eg, checkpoint inhibitors,
co-stimulatory agents etc.) or any grade immune-related AEs that
required immune suppressive therapy.
17) (Part A & Part B): Patients with intolerance to or who have had
a severe (>/=Grade 3) allergic or anaphylactic reaction to antibodies
or infused therapeutic proteins, or patients who have had a severe
allergic or anaphylactic reaction to any of the substances included in
the investigational product (including excipients).
18) (Part A & Part B): Patients with a previous history of
anthracycline treatment and are at risk of cardiac failure (New York
Heart Association [NYHA] Class II or above.
19) (Part A & Part B): Any one of the following currently or in the
previous 6 months: myocardial infarction, congenital long QT syndrome,
torsade¡¦s de points, arrhythmias (including sustained ventricular
tachyarrhythmia and ventricular fibrillation), and left anterior
hemiblock (bifascicular block), unstable angina, coronary/peripheral
artery bypass graft, symptomatic congestive heart failure (CHF New York
Heart Association class III or IV), cerebrovascular accident, transient
ischemic attack or symptomatic pulmonary embolism or other clinical
significant episode of thrombo-embolic disease*. Ongoing cardiac
dysrhythmias of NCI CTCAE grade >/=2, atrial fibrillation of any
grade, or QTcF interval >470 msec at screening (except in case of
right bundle branch block, these cases must be discussed with sponsor¡¦s
medical monitor).
20) (Continuation from #19) *Cases must be discussed in detail with
sponsor¡¦s medical monitor to judge eligibility.Anticoagulation (heparin
and trypsin-like serine protease (factor Xa) inhibitors only, no
vitamin-K antagonists) will be allowed if indicated.
21) (Part A & Part B): Participation in other interventional studies
within 28 days before the current study begins and/or during study
participation. Before joining Study B0601002, at least 28 days must have
passed from last systemic study therapy administration. Participation in
long term follow up is allowed if no procedures which may interfere with
the interpretation of study results will be performed.
22) (Part A only): Patients in the 0.01 mg/kg cohort must not be
</=50 kg in weight.
23) (Part B only): Patients that will receive 0.01 mg/kg PF-04518600
must not be </= 50 kg in weight.
24) (Part A & Part B): Pregnant female patients; breastfeeding
female patients (including patients who are weaning their infants).
25) (Part A & Part B): Other severe acute or chronic medical or
psychiatric condition, including recent (within the past year) or active
suicidal ideation or behavior, or laboratory abnormality that may
increase the risk associated with study participation or investigational
product administration or may interfere with the interpretation of study
results and, in the judgment of the investigator or sponsor¡¦s medical
monitor, would make the patient inappropriate for entry into this study.
26) (Part A & Part B): Patients who are investigational site staff
members directly involved in the conduct of the study and their family
members, site staff members otherwise supervised by the investigator, or
patients who are Pfizer employees directly involved in the conduct of
the study.